1. Field of the Invention
The present invention relates to polymer cantilevers that are useful in biosensor applications, and in particular to parylene cantilevers that are useful in such applications.
2. Background Art
Biosensors play a crucial role in disease diagnosis, drug discovery, environment monitoring, prevention of bio-terrorism, and the like. The biosensor usually consists of two parts: a molecular recognition element (receptor coating) and a transducer that converts the recognition event into different physical signals. Various transduction methods, based on thermal, mass, electrochemical and optical phenomena occurring during the biomolecular recognition event, have been implemented for biological sensing.
Recently, biosensors utilizing cantilever bending caused by surface stress change has attracted special attention. FIG. 1 provides a schematic demonstrating the operating principle of such cantilevers. Cantilever sensing system 10 includes micro-cantilever 12 mounted on substrate 14. Micro-cantilever 12 is immobilized with a probe layer of bio-specific molecules (e.g., probe single-stranded DNA) on side 16. The selective binding of target bio-molecules (e.g., complementary single-stranded DNA) to immobilized probe layer results in a surface stress change that causes a mechanical bending of the cantilever from position 18 to position 20 or vice versa. Accordingly, the existence of target biomolecules can be detected by monitoring the bending of the cantilever. Typically, the bending is monitored with an optical lever technique that includes laser 22 and photosensor 24. The bending of microcantilever 12 is detected as movement along direction 26 of laser beam 28 from along laser beam path 30 to path 32. The unique advantage of this prior art sensing scheme is that it is a label-free assay in that there is no need to label the target biomolecules with fluorescent dyes or radioisotopes.
The displacement of the cantilever tip can be described by the following equation:
      Δ    ⁢                  ⁢    z    =                    3        ⁢                  (                      1            -            v                    )                ⁢                  L          2                            EH        2              ⁢    Δ    ⁢                  ⁢    σ  where v is Poisson's ratio, E is Young's modulus, H is the cantilever thickness, L is the cantilever length and Δσ is the surface stress change generated by the adsorbed molecules. The surface stress generated by molecule recognition is usually very small. For instance, the DNA hybridization results in a surface stress change in the order of 10−3 N/m. So far, the majority of cantilever biosensors are fabricated using LPCVD (low pressure chemical vapor deposition) silicon nitride, with a Young's modulus between 260 GPa and 330 GPa, or silicon, with a Young's modulus of ˜160 GPa. For a typical nitride cantilever, 250 μm long, 200 μm wide, and 0.5 μm thick, the deflection of the cantilever tip caused by a 1×10−3 N/m surface stress is only ˜2 nm. The extremely low value for the deflection is the reason why the optical lever method is almost exclusively used to detect the cantilever bending as shown in FIG. 1.
The detection of DNA hybridization, DNA single-nucleotide mismatches, prostate-specific antigen (PSA), two cardiac biomarker proteins (creatin kinase and myoglobin), and glucose have been demonstrated using the optical cantilever method. Moreover, microcantilever based sensors have proven to be a very promising platform for a wide variety of biosensing applications. The cantilever sensor technique can be a universal platform for the detection of various specific biomolecular bindings such as DNA hybridization, DNA-RNA binding, antigen-antibody binding, protein-ligand binding, and DNA-protein binding since the cantilever motion is driven by free-energy change, which is universal for almost all specific biomolecular bindings.
Currently, the optical lever method is almost exclusively used to detect the nanoscale deflection of cantilevers in the literatures. Although the optical method offers excellent sensitivity, it has several intrinsic disadvantages. First, the system can not be miniaturized. Second, the optical system is expensive (a laser source and a photosensor with associated readout circuits can easily exceed $2000). Third, it is difficult to monitor large 2-D cantilever arrays using optical lever method.
Accordingly, it is desirable to provide a cantilever sensor that is inexpensive and capable of being miniaturized.